Observations of Spontaneous Size Stabilization of Surfactant-Coated Nanobubbles

Our study investigates a surprising observation of spontaneous size stabilization of surfactant-coated bulk nanobubbles (NBs) to a narrow size distribution. NBs are promising ultrasound imaging contrast agents due to their sub-micron size, prolonged circulation time and ability to extravasate into tumour tissue. Controlling the size distribution of NBs is critical in ultrasound imaging for enhancing acoustic sensitivity and producing more uniform signals. However, conventional filtering and size separation methods to isolate small size distributions of NBs may alter the NB surface chemistry and reduce signal output.

Here, we report the spontaneous size stabilization of NBs to a narrow diameter range of (100 - 300 nm) without external filtration or size separation. Using resonant mass measurement, the only technique capable of differentiating NBs from other negatively buoyant nanoparticles, and transmission electron microscopy, we observe an initially polydisperse (PDI = 0.5) NB population becoming less polydisperse (PDI = 0.2-0.3) over time. The decrease in the PDI of NBs over time occurs without significant loss in concentration, indicating that NBs are shrinking rather than dissolving or coalescing.

We propose that this process is a self-limiting process governed by surfactant saturation on the NB surface leading to a near-zero surface tension. Initially, differences in surface tensions and Laplace pressures across the bubble distribution drive large bubbles to shrink. As bubbles enter the sub-micron range, the surfactant shell eventually reaches a maximum surfactant areal density. At this point, the surface tension approaches near-zero and halts further bubble shrinkage. We suspect this near-zero surface tension occurs when bubbles shrink to the observed size ranges of 100 nm - 300 nm. Our findings provide a physical basis of the long-time stability of NBs for biomedical imaging.